This invention relates to a method and apparatus for the position sensitive detection and analysis of radioactivity in a fluid stream, and more particularly to such detection and analysis in gas and liquid chromatography.
Chromatography has been an important research tool for many years in a wide variety of applications. The principles of chromatography are well known to those of ordinary skill in the art. Essentially, a sample containing a mixture of constituent components, referred to herein as analytes, is introduced into a fluid stream. In a simple type of chromatographic apparatus, the fluid stream is brought into contact with a resin bed. The resin has been chemically or physically treated so as to selectively retard the passage of the analytes. The result is that the sample mixture is collimated, that is, separated into its discrete analytes. The fluid stream with the collimated sample then flows out, as an effluent stream, from the collimating means. The collimated effluent fluid stream is typically passed through a detector or analyzer which determines the presence, amount, and or type of analyte. The presence of a particular analyte can be depicted graphically as a peak on a chart. The timing and size of each peak provides significant information regarding the analyte.
While chromatographic techniques and technology have enjoyed great advances generally, one aspect of chromatography has not. This area is the detection and analysis of radioactive and radiolabelled analytes. Indeed, the current state of the art in this area has not changed greatly since the early 1970's except for the fairly peripheral advancements in the use of computers and integrated circuits.
The current method of radioactivity detection in gas chromatography is referred to as gas proportional counting (GPC). Typical of the state of the art in this regard is the original design of the Packard Model 894 counter used for GPC. In this instrument the effluent stream from the chromatograph contains or has added to it a quenched gas. The stream is then passed into a counting tube. In the counting tube is mounted a high voltage wire. Radioactive decay events, such as the emission of a beta particle or a gamma ray, create ions in the gas stream, which in turn is electrically detected via the wire. The events can be detected and counted to determine the presence and approximate amount of the radioactive analyte in the tube.
This technology has significant limitations. The wire in the counting tube is sensitive to background noise such as ambient radiation and radiation from internally deposited debris. The apparatus can be "tuned," that is, adjusted so as to increase efficiency, but is then sensitive to voltage and gas fluxes that may produce false readings. Typically, then, the instruments are not tuned in order to increase operational ease at the expense of analytical efficiency.
The resolution capability of this type of instrument also lags significantly behind the resolution capability of modern gas chromatography. Modern gas chromatography can separate and resolve many analyte peaks per minute. The state of the art GPC, however, can only recognize a single peak for all decay events occurring within the entire volume and length of the counting tube. Peak detection for radioactivity is thus limited to less than one per minute, making it impossible to correlate the radioactivity peak with the analyte peaks. Moreover, due to low counting efficiencies, quenching, detuning, and high background, detecting smaller radioactive peaks (for example, less than 250 disintegrations per minute (dpm)) is difficult. Thus a small but analytically important radiolabelled analyte may be completely missed or ignored by even modern GPC detectors.
Problems exist with radioactive assays performed with liquid chromatography also. In order to detect radioactive analytes, the liquid effluent stream from a liquid chromatograph must include or be mixed with liquid scintillation fluid. Decay events excite the liquid scintillation fluid to produce light, which can then be detected and measured. This process is expensive and inefficient. Relatively large amounts of scintillation fluid must be used and then safely disposed. Sample sizes typically must be larger, increasing the trouble and expense of obtaining the sample analyte.